Epilepsy & Behavior 37 (2014) 7–10
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Impact of family support on psychiatric disorders and seizure control in patients with juvenile myoclonic epilepsy☆ Sita Jayalakshmi a,⁎,1, Gaddamanugu Padmaja b,2, Sudhindra Vooturi a,1, Anand Bogaraju c, Mohandas Surath a,1 a b c
Department of Neurology, Krishna Institute of Medical Sciences, Minister Road, Secunderabad-03, Andhra Pradesh, India Department of Neurology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh, India Institute of Mental Health, Hyderabad, India
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Article history: Received 6 May 2014 Revised 18 May 2014 Accepted 23 May 2014 Available online xxxx Keywords: Juvenile myoclonic epilepsy Psychiatric comorbidities Family support Seizure control
a b s t r a c t Objective: Psychiatric disorders (PDs) are frequently observed in patients with juvenile myoclonic epilepsy (JME). In this study, we aimed to assess factors associated with PDs in patients with JME. Methods: Retrospective analysis of data of 90 consecutive patients with JME was performed. Assessment of DSM-IV Axis I clinical disorders was done using Structured Clinical Interview for Axis I. Diagnosis of PDs is made when the score exceeds the threshold provided by the DSM-IV. We also applied the Global Assessment of Functioning (GAF) scale which is part of the multiaxial evaluation of the DSM-IV (Axis-V). Using seizure frequency score at presentation, we classified subjects into controlled and uncontrolled groups. Results: In the current cohort, 29 (32.2%) patients were diagnosed with PDs. Fewer patients with PDs had family support (48.3% vs. 83.6%; p = 0.001). Lifetime prevalence of PDs was higher among patients with current PDs (96.6% vs. 18.0%; p b 0.0001). Subthreshold illness was not different between the groups (17.2% vs. 27.9%; p = 0.204). Mean GAF was higher in patients without PDs than in patients with PDs (89.19 ± 6.92 vs. 64.22 ± 9.76; p b 0.0001). Patients with PDs had lower seizure control (7.8% vs. 73.1%; p b 0.0001) compared with patients without PDs. Logistic regression analysis for factors associated with diagnosis of PDs revealed that none of the factors significantly affected the odds of seizure control. Patients with lack of family support had poor seizure control (0% vs. 36.9%; p b 0.0001); 51.7% of patients with JME with PDs reported lack of family support. Patients with family support had lower lifetime prevalence of PDs (30.8% vs. 76.0%; p b 0.0001), whereas patients with JME without family support had lower levels of education (8.0% vs. 35.4%; p = 0.009). Conclusion: Lack of family support is associated with poor seizure control and higher incidence of PDs in patients with JME. Lack of family support increases neither the odds of PDs nor seizure control. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Juvenile myoclonic epilepsy (JME) is the most common idiopathic, generalized epilepsy with onset around puberty [1]. Myoclonic jerks (MJs) with generalized tonic–clonic seizures (GTCSs) on awakening are the predominant seizure types; typical absences occur in about one-third of the patients. The interictal EEG is characterized by generalized spike–waves and polyspike–waves [2]. Lifestyle factors like stress, excess alcohol intake, sleep deprivation, and fatigue are known to be
☆ Funding: None. ⁎ Corresponding author at: Krishna Institute of Medical Sciences, 1-8-31/1, Minister Road, Secunderabad-500 003, Andhra Pradesh, India. Tel.: +91 9618117118; fax: +91 40 27840980. E-mail address: [email protected] (S. Jayalakshmi). 1 Tel.: +91 40 44185000. 2 Tel.: +91 40 23489143.
http://dx.doi.org/10.1016/j.yebeh.2014.05.020 1525-5050/© 2014 Elsevier Inc. All rights reserved.
precipitating factors in JME. Valproic acid (VPA) is the first drug of choice, and excellent response is seen in up to 80% of the patients with JME [3–6]. Other antiepileptic drugs (AEDs) such as lamotrigine, levetiracetam, topiramate, clobazam, and clonazepam can be used in patients with JME who are intolerant to VPA, who develop significant adverse reactions, or whose seizures are uncontrolled with VPA monotherapy. Patients with JME have been shown to have mild but characteristic behavioral problems [7] and cognitive impairments similar to those seen in patients with frontal lobe epilepsy [8]. These findings were reported in patients with JME based on the performance on the word fluency test and the Wisconsin card scoring test. Existence of psychiatric disorders (PDs) in patients with JME has been shown to be associated with drug resistance and may pose therapeutic problems in the management of these patients [5,9]. Interestingly, family support and size have been previously associated with generalized anxiety in population studies [10,11]. Importantly, parental behaviors and family cohesion influence drug compliance in children and adolescents with epilepsy
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[12–14]. Therefore, family support may influence the vicious cycle of psychiatric comorbidity and resistance to drugs in patients with JME. Observations in patients with JME in Asian populations have reported JME to be an underrecognized form of epilepsy [15]. Most of the research on JME in developing countries is observational with a focus on presenting the clinical spectrum. To the best of our knowledge, there is no available literature on psychiatric comorbidities in JME in the Indian population and, specifically, about the role of family support in patients with JME. Data available in other parts of the globe are hindered by lack of clinical psychometric assessment [16], lack of appropriate definitions [7], or insufficient sample sizes [17]. Although some researchers have attempted to overcome these shortcomings [18], it is not known if the same findings apply for the Indian population. 2. Materials and methods 2.1. Subject selection A retrospective analysis of clinical data of all the patients with diagnosis of JME, who were part of a larger epilepsy registry and had a follow-up for at least 3 years, was performed. The registry was maintained by the neurologist (SJ) who is part of the comprehensive epilepsy care program. The diagnosis and follow-up of JME were made by SJ. The diagnosis of JME was based on the International Classification of Epilepsies [1]. The inclusion criteria were as follows: (1) unequivocal clinical (historical) evidence of MJs predominantly on awakening with or without GTCSs and/or absence seizures; (2) absence of evidence of neurological or intellectual deficit; and (3) abnormal EEG in untreated patients with generalized spike and/or multiple spike–wave discharges. The exclusion criteria were the following: (1) patients with evidence of neurological or intellectual deficit and those with evidence of myoclonic jerks secondary to brain hypoxia, metabolic disease, and degenerative diseases; (2) nonavailability of at least one EEG record for review; and (3) noncompliance to AEDs as reported by the patient or one of the caregivers. Data of patients who satisfied all the inclusion criteria for diagnosis of JME were obtained with uniform protocol for data collection. Computed tomography (CT) and/or magnetic resonance imaging (MRI) of the brain were done as required. Psychiatric evaluation was performed in 90 consecutive patients with JME during the period from January 2008 to May 2009. They were interviewed by a psychiatrist (GP). The data collected also included relevant details about age, previous medical history, family history of epilepsy, social history, lifestyle, semiology, clinical presentation, compliance to medical management, reported family support, and prognosis. The study was approved by the institutional ethics committee. 2.2. Psychiatric assessment Assessment of DSM-IV Axis I clinical disorders was done using relevant Structured Clinical Interview for Axis I [19]. Structured Clinical Interview for DSM Disorders (SCID) scores are used to assess both current status and lifetime psychiatric status. It is based on a battery of screening questions and decisions leading to more specific questions. Each patient can have more than one psychiatric diagnosis in Axis I disorders. A diagnosis of psychiatric disorder is made when the score exceeds the threshold provided by the DSM-IV. We also applied Global Assessment of Functioning (GAF) scale, which is part of the multiaxial evaluation of the DSM-IV (Axis V) measuring a hypothetical mental illness continuum from 0 to 100. 2.3. Seizure control data Using seizure frequency score [20] at presentation, we classified subjects into controlled (score b 5, seizure-free with or without AEDs or those with only nondisabling nocturnal seizures) and uncontrolled (score N 5, having seizures in spite of AEDs). Review of the patient
records, input from the caregivers, and follow-up visits were also taken into account to assess compliance to treatment. 2.4. Statistical analysis The subjects were divided into two groups: primarily based on diagnosis of PDs and subsequently based on family support. Determining differences between the groups for continuous variables was done using the independent Student t-test after variance of data was corrected using the Levene test for equality of data variance. Determining differences between the groups for categorical variables was done using the chi-squared test. Variables that were significantly different between the groups were included for correlation analysis; r N 0.300 is reported. A logistic regression model to analyze association between variables significantly different between the groups with seizure control and PDs was built. A two-sided p b 0.05 was considered significant. All statistical analyses were done using SPSS 17.0 version for Windows, IBM Corporation, New York, USA. 3. Results The mean age of the study population was 25.1 years, with ages ranging from 15 to 40 years. Men constituted nearly 53% of the study population. There were no significant differences between patients diagnosed with PDs and those who were not diagnosed with PDs for age and gender. In the entire cohort of 90 patients, 24 patients had good control of seizures. Twenty-nine (32.2%) patients were diagnosed with PDs. When analyzed for differences between patients with diagnosis of PDs and those without diagnosis of PDs, there were no differences between the groups for gender, marital status, and literacy. Similarly, both groups did not differ regarding family history of PDs (10.3% vs. 13.1%; p = 1.000). However, fewer patients with PDs had family support (48.3% vs. 83.6%; p = 0.001). There were no differences between the groups for current employment (48.3% vs. 68.9%; p = 0.068) and the groups for skilled occupation (27.6% vs. 52.5%; p = 0.085). Lifetime prevalence of psychiatric illness was higher in patients with PDs than in those without PDs (96.6% vs. 18.0%; p b 0.0001). On the contrary, subthreshold illness was not significantly different between the groups (17.2% vs. 27.9%; p = 0.204). The differences between the groups for measured variables are summarized in Table 1. In the group with subthreshold PDs, three patients reported anxiety, two patients had obsessive–compulsive disorder, and four patients had somatoform manifestations. Among the patients with diagnosed PDs, three patients were alcohol-dependent, four patients had anxiety, two patients had dysthymia, three patients had MDD, and one patient reported OCD. A majority of 22 patients with PDs reported subthreshold Table 1 Differences between patients with juvenile myoclonic epilepsy with psychiatric disorders and patients with juvenile myoclonic epilepsy without psychiatric disorders. Serial Variable Number
Patients with PDs (n = 29)
Patients without PDs (n = 61)
1 2 3 4 5 6 7 8 9 10 11 12 13
25.28 ± 6.15 12 (41.4%) 13 (44.8%) 3 (10.3%) 14 (48.3%) 3 (10.3%) 8 (27.6%) 14 (48.3%) 28 (96.6%) 5 (17.2%) 6.84 ± 0.94 62.59 ± 9.22 0
24.54 ± 6.83 0.617 36 (59.0%) 0.175 22 (36.1%) 0.287 1 (1.6%) 0.206 51 (83.6%) 0.001 8 (13.1%) 1.000 32 (52.5%) 0.085 42 (68.9%) 0.068 11 (18.0%) b0.0001 17 (27.9%) 0.204 5.55 ± 2.21 0.007 75.64 ± 14.72 b0.0001 24 (39.3%) b0.0001
Age (years) Gender male (%) Married (%) Literate (%) Family support present (%) Family history of PDs (positive) Skilled employees (%) Currently working (%) Lifetime prevalence of PDs (%) Subthreshold PDs Seizure score GAF score Seizure control
p value
Abbreviations: PDs — psychiatric disorders. GAF — Global Assessment of Functioning scale.
S. Jayalakshmi et al. / Epilepsy & Behavior 37 (2014) 7–10 Table 2 Differences between patients with juvenile myoclonic epilepsy based on family support. Serial Variable Number
Patients without family support (n = 25)
Patients with p value family support (n = 65)
1 2 3 4
52.0 8.0 28.0 16.0
53.8 35.4 50.8 10.8
1.000 0.009 0.061 0.490
76.0
30.8
b0.0001
96.0
90.8
0.668
96.0 6.91 ± 0.92 61.60 ± 9.76 0
61.5 b0.001 5.59 ± 2.16 0.001 75.22 ± 14.31 b0.009 36.9 b0.0001
5 6 7 8 9 10
Gender male (%) Graduate patients (%) Skilled employees (%) Family history of PDs (%) Lifetime prevalence of PDs (%) Psychosocial problems (%) Current PDs (%) Seizure score GAF score Seizure control
Abbreviations: PDs — psychiatric disorders. GAF — Global Assessment of Functioning scale.
somatoform manifestations. Mean GAF was significantly higher in patients without PDs than in patients with PDs (89.19 ± 6.92 vs. 64.22 ± 9.76; p b 0.0001). The average seizure score was significantly higher in patients with PDs (6.69 ± 1.55 vs. 4.09 ± 1.75; p b 0.0001), consistent with the findings for low seizure control in these patients (7.8% vs. 73.1%; p b 0.0001). When analyzed for factors that were associated with PDs in the study population, GAF (r = −0.749; p b 0.0001), seizure score (r = 0.608; p b 0.0001), and seizure control (r = −0.669; p b 0.0001) showed strong and significant correlations with PDs. Logistic regression analysis for factors associated with seizure control revealed that, though the model assumed statistical significance (p b 0.0001), Cox–Snell R square value of 44.3%, and Nagelkerke's R square value of 64.6%, none of the factors (family support, current employment status, diagnosis of PDs, and lifetime prevalence of psychiatric illness) significantly affected the odds of seizure control. Similarly, when analyzed for factors associated with diagnosis of PDs, though the model assumed statistical significance (p b 0.0001), Cox–Snell R square value of 25.8%, and Nagelkerke's R square value of 36.9%, none of the factors (family support, current employment status, and lifetime prevalence of psychiatric illness) significantly affected the odds of seizure control. Subsequently, the study population was divided into patients with family support and those without family support. None of the patients who lacked family support had seizure control (0% vs. 36.9%; p b 0.0001), and 51.7% of patients with JME with PDs reported lack of family support. The mean seizure score was higher in patients without family support than in those with family support (6.91 ± 0.92 vs. 5.59 ± 2.16; p = 0.001). Moreover, the GAF score was significantly lower in patients without family support (61.60 ± 9.76 vs. 75.59 ±14.31; p = 0.009). Patients with family support had a lower lifetime prevalence of PDs (30.8% vs. 76.0%; p b 0.0001), but no differences between the groups were observed for current psychosocial problems (96.0% vs. 90.8%; p = 0.668). A lower percentage of patients without family support were educated through graduation (8.0% vs. 35.4%; p = 0.009). Similarly, lesser number of patients without family support were employed in skilled employment (28% vs. 50.8%; p = 0.0612). The differences between patients with family support and those without family support are summarized in Table 2.
4. Discussion There is a widespread consensus that psychiatric aspects of JME and clinical prognosis are interrelated. The findings of our study suggest that patients with JME diagnosed with PDs have lower rates of reported family support. Lack of family support is associated with poor seizure control and higher incidence of PDs in patients with JME. However, lack of family support does not increase the odds of PDs in patients
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with JME. Further research analyzing factors that predispose PDs in patients with JME is necessary. Most of the studies to date have reported rates of 26.5% to 47% [18,21,22] for PDs in patients with JME. In the current study, we found a similar prevalence of psychiatric comorbidities such that 32.2% of the study population was diagnosed with PDs. Epilepsy has consistently been associated with psychiatric morbidity in the past [23,24], but the reported prevalence has been as low as 19% [25] to as high as 80% [17]. This discrepancy in prevalence may be due to the varied sampling of patients with epilepsy, variability in the diagnosis of PDs, and retrospective design of the study. Since the present study was conducted at a tertiary epilepsy referral care center, the high prevalence of PDs among the patients with JME may hold consistent with the general population with JME in India. Moreover, the rate of unemployment (37%) and the average GAF score (69.5) are similar to those reported by de Araujo Filho et al. [26]. Microscopic structural abnormalities in the frontal cortices of patients with JME have been described in autopsy studies [27,28], studies using magnetic resonance imaging [29], and positron emission tomography [30]. Personality disorders in patients with JME have previously been attributed to frontal lobe deficits by Devinsky et al. [31] who found impairment in the battery of tests involving concept formation, cognition, planning, and organization. Trinka et al. [18] have previously suggested that stigmatization of patients with JME due to repeated childhood seizures may not be the reason for increased prevalence of PDs but rather due to coexisting subtle abnormalities in the frontal lobe which could serve as a common base for both epilepsy and PDs in patients with JME. The key finding of the current study is the association between lack of family support and PDs in patients with JME. Moreover, education and skilled occupations are significantly lower in patients without family support and, therefore, increased chances of lifelong prevalence of PDs in these patients. These findings may probably be due to previously reported lower global social adjustment scores in patients with JME than in healthy controls [32]. Moreover, Dunn et al. have shown in the past that psychiatric symptoms like depression in adolescents are highly influenced by satisfaction in family relationships [33]. Neuropsychological profiling of patients with JME in comparison with their healthy siblings has previously shown that significant impairment in social, occupational, and academic performance in patients with JME may be attributed to impairments in verbal and executive functioning [34]. The genes for ‘negativistic/irresponsible’ behavior may underlie both the lack of parental support and the nonadherence by patients. However, the role of genetics is debatable, and further research in this direction is required. Psychiatric symptoms, whether preceding the epilepsy or forming the clinical spectrum of epilepsy, are often underdiagnosed and untreated [35]. Unfortunately, coexisting PDs negatively affect the quality of life in these patients [36]. The consistency of these findings in patients with JME is largely unknown. Cohesive family atmosphere has been shown to increase adherence to medications by 1.74 times in patients on prescriptions for PDs [37]. The same study has also shown that lack of cohesive family environment reduces compliance to medications by 1.53 times in these patients. In the current study, we have demonstrated that patients with lack of family support had lower levels of education and skilled employment. Impaired skill and executive functions may perhaps lead to noncompliance to medications and, therefore, lower seizure control. Lower seizure control, hence, leads to higher lifetime prevalence of PDs in patients with JME without family support, as reported in our study. Moreover, lower social adjustment score further complicates this vicious cycle of poor seizure control in patients with JME. Interventions to prevent clinical depression and PDs in adolescents without epilepsies have been successful [38]. Encouragingly, Martinovic et al. have shown in 14 patients with JME that a structured six-week counseling program aimed at eliminating seizure precipitants reduces non-adaptive responses like anxiety and also lowers the rates of
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relapses [39]. However, results across studies are inconsistent probably because of small numbers of participants in these studies and the fact that the seizure-free state contributes the most of any factor towards improved quality of life and psychosocial well-being in adolescents with epilepsies [36,40,41]. Importantly, the clinical implications of these observations on social adjustment like family cohesiveness need to be explored. The interaction between lack of family support and PDs and its effect on seizure control in patients with JME warrants further research. 5. Limitations The present study is from a tertiary epilepsy referral care center, and the stringent inclusion criteria might explain the higher number of patients with lack of seizure control. However, this may have not influenced the results as the findings seem plausible in patients with JME. 6. Conclusion Nearly one-third of patients with JME have coexisting PDs. A high number of patients with JME with PDs reported lack of family support. Though lack of family support was associated with PDs in patients with JME, it increased neither the odds of PDs nor seizure control in these patients. Lack of social adjustment in these patients may possibly explain the reported high rates of lack of family support. Conflict of interest None of the authors has any conflict of interest to disclose. Author contribution Data collection and interpretation: Gaddamanugu Padmaja and Dr. Sita Jayalakshmi; study concept and design: Dr. Sita Jayalakshmi and Dr. Anand Bogaraju; statistical analysis and interpretation of the data: Dr. Sudhindra Vooturi; and critical revision of the manuscript: Dr. Surath Mohandas. References [1] Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1989;30:389–99. [2] Aliberti V, Grunewald RA, Panayiotopoulos CP, Chroni E. Focal electroencephalographic abnormalities in juvenile myoclonic epilepsy. Epilepsia 1994;35:297–301. [3] Delgado-Escueta AV, Enrile-Bacsal F. Juvenile myoclonic epilepsy of Janz. Neurology 1984;34:285–94. [4] Panayiotopoulos CP, Obeid T, Tahan AR. Juvenile myoclonic epilepsy: a 5-year prospective study. Epilepsia 1994;35:285–96. [5] Gelisse P, Genton P, Thomas P, Rey M, Samuelian JC, Dravet C. Clinical factors of drug resistance in juvenile myoclonic epilepsy. J Neurol Neurosurg Psychiatry 2001;70: 240–3. [6] Trinka E, Baumgartner S, Unterberger I, Unterrainer J, Luef G, Haberlandt E, et al. Long-term prognosis for childhood and juvenile absence epilepsy. J Neurol 2004;251:1235–41. [7] Lund M, Reintoft H, Simonsen N. A controlled sociological and psychological study on patients with juvenile myoclonus epilepsy. Nervenarzt 1976;47:708–12. [8] Swartz BE, Simpkins F, Halgren E, Mandelkern M, Brown C, Krisdakumtorn T, et al. Visual working memory in primary generalized epilepsy: an 18FDG-PET study. Neurology 1996;47:1203–12. [9] Jayalakshmi S, Vooturi S, Bana AK, Sailaja S, Somayajula S, Mohandas S. Factors associated with lack of response to valproic acid monotherapy in juvenile myoclonic epilepsy. Seizure 2014 Apr 5. http://dx.doi.org/10.1016/j.seizure.2014.03.017 pii: S1059-1311(14)00099-5. [Electronic publication ahead of print]. [10] Ai AL, Weiss SI, Fincham FD. Family factors contribute to general anxiety disorder and suicidal ideation among Latina Americans. Womens Health Issues 2014 May– Jun;24(3):e345-52. http://dx.doi.org/10.1016/j.whi.2014.02.008 [Electronic publication ahead of print 2014 Mar 28]. [11] Cheng JK, Fancher TL, Ratanasen M, Conner KR, Duberstein PR, Sue S, et al. Lifetime suicidal ideation and suicide attempts in Asian Americans. Asian Am J Psychol 2010 Mar;1(1):18–30.
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Impact of family support on psychiatric disorders and seizure control in patients with juvenile myoclonic epilepsy☆ Sita Jayalakshmi a,⁎,1, Gaddamanugu Padmaja b,2, Sudhindra Vooturi a,1, Anand Bogaraju c, Mohandas Surath a,1 a b c
Department of Neurology, Krishna Institute of Medical Sciences, Minister Road, Secunderabad-03, Andhra Pradesh, India Department of Neurology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh, India Institute of Mental Health, Hyderabad, India
a r t i c l e
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Article history: Received 6 May 2014 Revised 18 May 2014 Accepted 23 May 2014 Available online xxxx Keywords: Juvenile myoclonic epilepsy Psychiatric comorbidities Family support Seizure control
a b s t r a c t Objective: Psychiatric disorders (PDs) are frequently observed in patients with juvenile myoclonic epilepsy (JME). In this study, we aimed to assess factors associated with PDs in patients with JME. Methods: Retrospective analysis of data of 90 consecutive patients with JME was performed. Assessment of DSM-IV Axis I clinical disorders was done using Structured Clinical Interview for Axis I. Diagnosis of PDs is made when the score exceeds the threshold provided by the DSM-IV. We also applied the Global Assessment of Functioning (GAF) scale which is part of the multiaxial evaluation of the DSM-IV (Axis-V). Using seizure frequency score at presentation, we classified subjects into controlled and uncontrolled groups. Results: In the current cohort, 29 (32.2%) patients were diagnosed with PDs. Fewer patients with PDs had family support (48.3% vs. 83.6%; p = 0.001). Lifetime prevalence of PDs was higher among patients with current PDs (96.6% vs. 18.0%; p b 0.0001). Subthreshold illness was not different between the groups (17.2% vs. 27.9%; p = 0.204). Mean GAF was higher in patients without PDs than in patients with PDs (89.19 ± 6.92 vs. 64.22 ± 9.76; p b 0.0001). Patients with PDs had lower seizure control (7.8% vs. 73.1%; p b 0.0001) compared with patients without PDs. Logistic regression analysis for factors associated with diagnosis of PDs revealed that none of the factors significantly affected the odds of seizure control. Patients with lack of family support had poor seizure control (0% vs. 36.9%; p b 0.0001); 51.7% of patients with JME with PDs reported lack of family support. Patients with family support had lower lifetime prevalence of PDs (30.8% vs. 76.0%; p b 0.0001), whereas patients with JME without family support had lower levels of education (8.0% vs. 35.4%; p = 0.009). Conclusion: Lack of family support is associated with poor seizure control and higher incidence of PDs in patients with JME. Lack of family support increases neither the odds of PDs nor seizure control. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Juvenile myoclonic epilepsy (JME) is the most common idiopathic, generalized epilepsy with onset around puberty [1]. Myoclonic jerks (MJs) with generalized tonic–clonic seizures (GTCSs) on awakening are the predominant seizure types; typical absences occur in about one-third of the patients. The interictal EEG is characterized by generalized spike–waves and polyspike–waves [2]. Lifestyle factors like stress, excess alcohol intake, sleep deprivation, and fatigue are known to be
☆ Funding: None. ⁎ Corresponding author at: Krishna Institute of Medical Sciences, 1-8-31/1, Minister Road, Secunderabad-500 003, Andhra Pradesh, India. Tel.: +91 9618117118; fax: +91 40 27840980. E-mail address: [email protected] (S. Jayalakshmi). 1 Tel.: +91 40 44185000. 2 Tel.: +91 40 23489143.
http://dx.doi.org/10.1016/j.yebeh.2014.05.020 1525-5050/© 2014 Elsevier Inc. All rights reserved.
precipitating factors in JME. Valproic acid (VPA) is the first drug of choice, and excellent response is seen in up to 80% of the patients with JME [3–6]. Other antiepileptic drugs (AEDs) such as lamotrigine, levetiracetam, topiramate, clobazam, and clonazepam can be used in patients with JME who are intolerant to VPA, who develop significant adverse reactions, or whose seizures are uncontrolled with VPA monotherapy. Patients with JME have been shown to have mild but characteristic behavioral problems [7] and cognitive impairments similar to those seen in patients with frontal lobe epilepsy [8]. These findings were reported in patients with JME based on the performance on the word fluency test and the Wisconsin card scoring test. Existence of psychiatric disorders (PDs) in patients with JME has been shown to be associated with drug resistance and may pose therapeutic problems in the management of these patients [5,9]. Interestingly, family support and size have been previously associated with generalized anxiety in population studies [10,11]. Importantly, parental behaviors and family cohesion influence drug compliance in children and adolescents with epilepsy
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[12–14]. Therefore, family support may influence the vicious cycle of psychiatric comorbidity and resistance to drugs in patients with JME. Observations in patients with JME in Asian populations have reported JME to be an underrecognized form of epilepsy [15]. Most of the research on JME in developing countries is observational with a focus on presenting the clinical spectrum. To the best of our knowledge, there is no available literature on psychiatric comorbidities in JME in the Indian population and, specifically, about the role of family support in patients with JME. Data available in other parts of the globe are hindered by lack of clinical psychometric assessment [16], lack of appropriate definitions [7], or insufficient sample sizes [17]. Although some researchers have attempted to overcome these shortcomings [18], it is not known if the same findings apply for the Indian population. 2. Materials and methods 2.1. Subject selection A retrospective analysis of clinical data of all the patients with diagnosis of JME, who were part of a larger epilepsy registry and had a follow-up for at least 3 years, was performed. The registry was maintained by the neurologist (SJ) who is part of the comprehensive epilepsy care program. The diagnosis and follow-up of JME were made by SJ. The diagnosis of JME was based on the International Classification of Epilepsies [1]. The inclusion criteria were as follows: (1) unequivocal clinical (historical) evidence of MJs predominantly on awakening with or without GTCSs and/or absence seizures; (2) absence of evidence of neurological or intellectual deficit; and (3) abnormal EEG in untreated patients with generalized spike and/or multiple spike–wave discharges. The exclusion criteria were the following: (1) patients with evidence of neurological or intellectual deficit and those with evidence of myoclonic jerks secondary to brain hypoxia, metabolic disease, and degenerative diseases; (2) nonavailability of at least one EEG record for review; and (3) noncompliance to AEDs as reported by the patient or one of the caregivers. Data of patients who satisfied all the inclusion criteria for diagnosis of JME were obtained with uniform protocol for data collection. Computed tomography (CT) and/or magnetic resonance imaging (MRI) of the brain were done as required. Psychiatric evaluation was performed in 90 consecutive patients with JME during the period from January 2008 to May 2009. They were interviewed by a psychiatrist (GP). The data collected also included relevant details about age, previous medical history, family history of epilepsy, social history, lifestyle, semiology, clinical presentation, compliance to medical management, reported family support, and prognosis. The study was approved by the institutional ethics committee. 2.2. Psychiatric assessment Assessment of DSM-IV Axis I clinical disorders was done using relevant Structured Clinical Interview for Axis I [19]. Structured Clinical Interview for DSM Disorders (SCID) scores are used to assess both current status and lifetime psychiatric status. It is based on a battery of screening questions and decisions leading to more specific questions. Each patient can have more than one psychiatric diagnosis in Axis I disorders. A diagnosis of psychiatric disorder is made when the score exceeds the threshold provided by the DSM-IV. We also applied Global Assessment of Functioning (GAF) scale, which is part of the multiaxial evaluation of the DSM-IV (Axis V) measuring a hypothetical mental illness continuum from 0 to 100. 2.3. Seizure control data Using seizure frequency score [20] at presentation, we classified subjects into controlled (score b 5, seizure-free with or without AEDs or those with only nondisabling nocturnal seizures) and uncontrolled (score N 5, having seizures in spite of AEDs). Review of the patient
records, input from the caregivers, and follow-up visits were also taken into account to assess compliance to treatment. 2.4. Statistical analysis The subjects were divided into two groups: primarily based on diagnosis of PDs and subsequently based on family support. Determining differences between the groups for continuous variables was done using the independent Student t-test after variance of data was corrected using the Levene test for equality of data variance. Determining differences between the groups for categorical variables was done using the chi-squared test. Variables that were significantly different between the groups were included for correlation analysis; r N 0.300 is reported. A logistic regression model to analyze association between variables significantly different between the groups with seizure control and PDs was built. A two-sided p b 0.05 was considered significant. All statistical analyses were done using SPSS 17.0 version for Windows, IBM Corporation, New York, USA. 3. Results The mean age of the study population was 25.1 years, with ages ranging from 15 to 40 years. Men constituted nearly 53% of the study population. There were no significant differences between patients diagnosed with PDs and those who were not diagnosed with PDs for age and gender. In the entire cohort of 90 patients, 24 patients had good control of seizures. Twenty-nine (32.2%) patients were diagnosed with PDs. When analyzed for differences between patients with diagnosis of PDs and those without diagnosis of PDs, there were no differences between the groups for gender, marital status, and literacy. Similarly, both groups did not differ regarding family history of PDs (10.3% vs. 13.1%; p = 1.000). However, fewer patients with PDs had family support (48.3% vs. 83.6%; p = 0.001). There were no differences between the groups for current employment (48.3% vs. 68.9%; p = 0.068) and the groups for skilled occupation (27.6% vs. 52.5%; p = 0.085). Lifetime prevalence of psychiatric illness was higher in patients with PDs than in those without PDs (96.6% vs. 18.0%; p b 0.0001). On the contrary, subthreshold illness was not significantly different between the groups (17.2% vs. 27.9%; p = 0.204). The differences between the groups for measured variables are summarized in Table 1. In the group with subthreshold PDs, three patients reported anxiety, two patients had obsessive–compulsive disorder, and four patients had somatoform manifestations. Among the patients with diagnosed PDs, three patients were alcohol-dependent, four patients had anxiety, two patients had dysthymia, three patients had MDD, and one patient reported OCD. A majority of 22 patients with PDs reported subthreshold Table 1 Differences between patients with juvenile myoclonic epilepsy with psychiatric disorders and patients with juvenile myoclonic epilepsy without psychiatric disorders. Serial Variable Number
Patients with PDs (n = 29)
Patients without PDs (n = 61)
1 2 3 4 5 6 7 8 9 10 11 12 13
25.28 ± 6.15 12 (41.4%) 13 (44.8%) 3 (10.3%) 14 (48.3%) 3 (10.3%) 8 (27.6%) 14 (48.3%) 28 (96.6%) 5 (17.2%) 6.84 ± 0.94 62.59 ± 9.22 0
24.54 ± 6.83 0.617 36 (59.0%) 0.175 22 (36.1%) 0.287 1 (1.6%) 0.206 51 (83.6%) 0.001 8 (13.1%) 1.000 32 (52.5%) 0.085 42 (68.9%) 0.068 11 (18.0%) b0.0001 17 (27.9%) 0.204 5.55 ± 2.21 0.007 75.64 ± 14.72 b0.0001 24 (39.3%) b0.0001
Age (years) Gender male (%) Married (%) Literate (%) Family support present (%) Family history of PDs (positive) Skilled employees (%) Currently working (%) Lifetime prevalence of PDs (%) Subthreshold PDs Seizure score GAF score Seizure control
p value
Abbreviations: PDs — psychiatric disorders. GAF — Global Assessment of Functioning scale.
S. Jayalakshmi et al. / Epilepsy & Behavior 37 (2014) 7–10 Table 2 Differences between patients with juvenile myoclonic epilepsy based on family support. Serial Variable Number
Patients without family support (n = 25)
Patients with p value family support (n = 65)
1 2 3 4
52.0 8.0 28.0 16.0
53.8 35.4 50.8 10.8
1.000 0.009 0.061 0.490
76.0
30.8
b0.0001
96.0
90.8
0.668
96.0 6.91 ± 0.92 61.60 ± 9.76 0
61.5 b0.001 5.59 ± 2.16 0.001 75.22 ± 14.31 b0.009 36.9 b0.0001
5 6 7 8 9 10
Gender male (%) Graduate patients (%) Skilled employees (%) Family history of PDs (%) Lifetime prevalence of PDs (%) Psychosocial problems (%) Current PDs (%) Seizure score GAF score Seizure control
Abbreviations: PDs — psychiatric disorders. GAF — Global Assessment of Functioning scale.
somatoform manifestations. Mean GAF was significantly higher in patients without PDs than in patients with PDs (89.19 ± 6.92 vs. 64.22 ± 9.76; p b 0.0001). The average seizure score was significantly higher in patients with PDs (6.69 ± 1.55 vs. 4.09 ± 1.75; p b 0.0001), consistent with the findings for low seizure control in these patients (7.8% vs. 73.1%; p b 0.0001). When analyzed for factors that were associated with PDs in the study population, GAF (r = −0.749; p b 0.0001), seizure score (r = 0.608; p b 0.0001), and seizure control (r = −0.669; p b 0.0001) showed strong and significant correlations with PDs. Logistic regression analysis for factors associated with seizure control revealed that, though the model assumed statistical significance (p b 0.0001), Cox–Snell R square value of 44.3%, and Nagelkerke's R square value of 64.6%, none of the factors (family support, current employment status, diagnosis of PDs, and lifetime prevalence of psychiatric illness) significantly affected the odds of seizure control. Similarly, when analyzed for factors associated with diagnosis of PDs, though the model assumed statistical significance (p b 0.0001), Cox–Snell R square value of 25.8%, and Nagelkerke's R square value of 36.9%, none of the factors (family support, current employment status, and lifetime prevalence of psychiatric illness) significantly affected the odds of seizure control. Subsequently, the study population was divided into patients with family support and those without family support. None of the patients who lacked family support had seizure control (0% vs. 36.9%; p b 0.0001), and 51.7% of patients with JME with PDs reported lack of family support. The mean seizure score was higher in patients without family support than in those with family support (6.91 ± 0.92 vs. 5.59 ± 2.16; p = 0.001). Moreover, the GAF score was significantly lower in patients without family support (61.60 ± 9.76 vs. 75.59 ±14.31; p = 0.009). Patients with family support had a lower lifetime prevalence of PDs (30.8% vs. 76.0%; p b 0.0001), but no differences between the groups were observed for current psychosocial problems (96.0% vs. 90.8%; p = 0.668). A lower percentage of patients without family support were educated through graduation (8.0% vs. 35.4%; p = 0.009). Similarly, lesser number of patients without family support were employed in skilled employment (28% vs. 50.8%; p = 0.0612). The differences between patients with family support and those without family support are summarized in Table 2.
4. Discussion There is a widespread consensus that psychiatric aspects of JME and clinical prognosis are interrelated. The findings of our study suggest that patients with JME diagnosed with PDs have lower rates of reported family support. Lack of family support is associated with poor seizure control and higher incidence of PDs in patients with JME. However, lack of family support does not increase the odds of PDs in patients
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with JME. Further research analyzing factors that predispose PDs in patients with JME is necessary. Most of the studies to date have reported rates of 26.5% to 47% [18,21,22] for PDs in patients with JME. In the current study, we found a similar prevalence of psychiatric comorbidities such that 32.2% of the study population was diagnosed with PDs. Epilepsy has consistently been associated with psychiatric morbidity in the past [23,24], but the reported prevalence has been as low as 19% [25] to as high as 80% [17]. This discrepancy in prevalence may be due to the varied sampling of patients with epilepsy, variability in the diagnosis of PDs, and retrospective design of the study. Since the present study was conducted at a tertiary epilepsy referral care center, the high prevalence of PDs among the patients with JME may hold consistent with the general population with JME in India. Moreover, the rate of unemployment (37%) and the average GAF score (69.5) are similar to those reported by de Araujo Filho et al. [26]. Microscopic structural abnormalities in the frontal cortices of patients with JME have been described in autopsy studies [27,28], studies using magnetic resonance imaging [29], and positron emission tomography [30]. Personality disorders in patients with JME have previously been attributed to frontal lobe deficits by Devinsky et al. [31] who found impairment in the battery of tests involving concept formation, cognition, planning, and organization. Trinka et al. [18] have previously suggested that stigmatization of patients with JME due to repeated childhood seizures may not be the reason for increased prevalence of PDs but rather due to coexisting subtle abnormalities in the frontal lobe which could serve as a common base for both epilepsy and PDs in patients with JME. The key finding of the current study is the association between lack of family support and PDs in patients with JME. Moreover, education and skilled occupations are significantly lower in patients without family support and, therefore, increased chances of lifelong prevalence of PDs in these patients. These findings may probably be due to previously reported lower global social adjustment scores in patients with JME than in healthy controls [32]. Moreover, Dunn et al. have shown in the past that psychiatric symptoms like depression in adolescents are highly influenced by satisfaction in family relationships [33]. Neuropsychological profiling of patients with JME in comparison with their healthy siblings has previously shown that significant impairment in social, occupational, and academic performance in patients with JME may be attributed to impairments in verbal and executive functioning [34]. The genes for ‘negativistic/irresponsible’ behavior may underlie both the lack of parental support and the nonadherence by patients. However, the role of genetics is debatable, and further research in this direction is required. Psychiatric symptoms, whether preceding the epilepsy or forming the clinical spectrum of epilepsy, are often underdiagnosed and untreated [35]. Unfortunately, coexisting PDs negatively affect the quality of life in these patients [36]. The consistency of these findings in patients with JME is largely unknown. Cohesive family atmosphere has been shown to increase adherence to medications by 1.74 times in patients on prescriptions for PDs [37]. The same study has also shown that lack of cohesive family environment reduces compliance to medications by 1.53 times in these patients. In the current study, we have demonstrated that patients with lack of family support had lower levels of education and skilled employment. Impaired skill and executive functions may perhaps lead to noncompliance to medications and, therefore, lower seizure control. Lower seizure control, hence, leads to higher lifetime prevalence of PDs in patients with JME without family support, as reported in our study. Moreover, lower social adjustment score further complicates this vicious cycle of poor seizure control in patients with JME. Interventions to prevent clinical depression and PDs in adolescents without epilepsies have been successful [38]. Encouragingly, Martinovic et al. have shown in 14 patients with JME that a structured six-week counseling program aimed at eliminating seizure precipitants reduces non-adaptive responses like anxiety and also lowers the rates of
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relapses [39]. However, results across studies are inconsistent probably because of small numbers of participants in these studies and the fact that the seizure-free state contributes the most of any factor towards improved quality of life and psychosocial well-being in adolescents with epilepsies [36,40,41]. Importantly, the clinical implications of these observations on social adjustment like family cohesiveness need to be explored. The interaction between lack of family support and PDs and its effect on seizure control in patients with JME warrants further research. 5. Limitations The present study is from a tertiary epilepsy referral care center, and the stringent inclusion criteria might explain the higher number of patients with lack of seizure control. However, this may have not influenced the results as the findings seem plausible in patients with JME. 6. Conclusion Nearly one-third of patients with JME have coexisting PDs. A high number of patients with JME with PDs reported lack of family support. Though lack of family support was associated with PDs in patients with JME, it increased neither the odds of PDs nor seizure control in these patients. Lack of social adjustment in these patients may possibly explain the reported high rates of lack of family support. Conflict of interest None of the authors has any conflict of interest to disclose. Author contribution Data collection and interpretation: Gaddamanugu Padmaja and Dr. Sita Jayalakshmi; study concept and design: Dr. Sita Jayalakshmi and Dr. Anand Bogaraju; statistical analysis and interpretation of the data: Dr. Sudhindra Vooturi; and critical revision of the manuscript: Dr. Surath Mohandas. References [1] Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1989;30:389–99. [2] Aliberti V, Grunewald RA, Panayiotopoulos CP, Chroni E. Focal electroencephalographic abnormalities in juvenile myoclonic epilepsy. Epilepsia 1994;35:297–301. [3] Delgado-Escueta AV, Enrile-Bacsal F. Juvenile myoclonic epilepsy of Janz. Neurology 1984;34:285–94. [4] Panayiotopoulos CP, Obeid T, Tahan AR. Juvenile myoclonic epilepsy: a 5-year prospective study. Epilepsia 1994;35:285–96. [5] Gelisse P, Genton P, Thomas P, Rey M, Samuelian JC, Dravet C. Clinical factors of drug resistance in juvenile myoclonic epilepsy. J Neurol Neurosurg Psychiatry 2001;70: 240–3. [6] Trinka E, Baumgartner S, Unterberger I, Unterrainer J, Luef G, Haberlandt E, et al. Long-term prognosis for childhood and juvenile absence epilepsy. J Neurol 2004;251:1235–41. [7] Lund M, Reintoft H, Simonsen N. A controlled sociological and psychological study on patients with juvenile myoclonus epilepsy. Nervenarzt 1976;47:708–12. [8] Swartz BE, Simpkins F, Halgren E, Mandelkern M, Brown C, Krisdakumtorn T, et al. Visual working memory in primary generalized epilepsy: an 18FDG-PET study. Neurology 1996;47:1203–12. [9] Jayalakshmi S, Vooturi S, Bana AK, Sailaja S, Somayajula S, Mohandas S. Factors associated with lack of response to valproic acid monotherapy in juvenile myoclonic epilepsy. Seizure 2014 Apr 5. http://dx.doi.org/10.1016/j.seizure.2014.03.017 pii: S1059-1311(14)00099-5. [Electronic publication ahead of print]. [10] Ai AL, Weiss SI, Fincham FD. Family factors contribute to general anxiety disorder and suicidal ideation among Latina Americans. Womens Health Issues 2014 May– Jun;24(3):e345-52. http://dx.doi.org/10.1016/j.whi.2014.02.008 [Electronic publication ahead of print 2014 Mar 28]. [11] Cheng JK, Fancher TL, Ratanasen M, Conner KR, Duberstein PR, Sue S, et al. Lifetime suicidal ideation and suicide attempts in Asian Americans. Asian Am J Psychol 2010 Mar;1(1):18–30.
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